Sanfilippo syndrome A is a neurodegenerative condition caused by a genetic error in metabolism: because of a missing enzyme, long-chained sugar molecules cannot be broken down. Toxic substrates accumulate in cells, causing a rapid cognitive decline and, later, motor decline. Most affected children die in their teens or earlier.

There is no treatment, and when Karen Aiach’s daughter Ornella was diagnosed with Sanfilippo syndrome A, no companies were even working on the disease.

As a mother, Aiach could not accept that.

In 2009, she left her financial career to co-found her own biotech company in her native France. With Aiach as CEO, Lysogene has raised $30 million, according to the Boston Business Journal. The company is poised to conduct its second clinical treatment trial for Sanfilippo syndrome.

But back in 2005, when Ornella was a baby, Aiach was overcome with hopelessness. “You’re just suffocating, you’re overwhelmed by the feeling of unfairness, you feel like you’re in a bottle,” she said in a keynote last week at Harvard Medical School’s conference Precision Medicine 2016: Rogue Therapeutics.

Correcting the Sanfilippo defect

As Ornella got older, she lost her language skills. It took most of Aiach’s energy to manage Ornella’s hyperactivity and compulsive behavior. Things were breaking in the house. And Ornella barely slept. “This disease is absolutely exhausting for the child and family,” says Aiach.

Aiach began gathering information on Sanfilippo syndrome A (also known as mucopolysaccharidosis type IIIA or MPS III), joining a growing cadre of citizen scientists.

“My unique purpose was to try to put together a program to find a cure for that disease, no matter what the clinicians said,” she recounted. “Because I was not a scientist, I could ask any question I wanted.”

She learned that Ornella had a genetic mutation causing a deficiency of the enzyme sulfamidase. Could the enzyme somehow be replaced?

Aiaich was introduced to Olivier Danos, PhD, now senior vice president of gene therapy at Biogen Idec. Danos co-founded Lysogene with Aiach in 2009 and remains its senior scientific advisor.

Because of the difficulty of getting effective drugs across the blood-brain barrier, Danos proposed introducing a gene therapy vector into the brain. The working gene would be taken up by neural cells and “act as an enzyme factory,” Aiach said.

In 2010, Lysogene received orphan designation for its product, LYS-SAF-302, in the European Union. In 2011, a clinical Phase I/II trial was approved in France and the first four patients were treated, including Ornella.

The treatment entailed a two-hour operation to inject the gene therapy vector directly into the brain through a series of small holes in the skull. “We have to be willing to consider very innovative approaches, even a neurosurgical one,” said Aiach.

Lysogene’s goal now is to become the premier gene therapy company for central nervous system disorders, bringing together small biotechs focused on rare diseases and large, well-resourced pharmaceutical companies.

“You have to have a strong focus,” Aiach advised other would-be parent entrepreneurs. “It’s important to be very curious, never to be shy and to ask the questions that you need to ask.”